The University of Iowa Specialized Center of Research (SCOR) in Osteoarthritis (OA) will support and coordinate a multidisciplinary group of experienced investigators in clinical, bioengineering, cell and molecular biology research to advance understanding of the pathogenesis of post-traumatic OA, and develop innovative approaches for preventing and treating this disease. Joint trauma dramatically increases the risk for development of OA. Yet, little work has been done on the pathogenesis and prevention of post-traumatic OA. For these reasons, a clear and urgent need exists to improve the understanding of this common and disabling disorder and our ability to prevent and treat it. The human ankle joint provides a unique opportunity for the study of post-traumatic OA because of the low risk of primary OA and the relatively high risk of post-traumatic OA. This SCOR will test the hypotheses that: 1) exceeding critical levels of acute energy absorption and chronic articular surface contact stress causes post-traumatic ankle OA, 2) the risk of OA following joint trauma increases with age as a result of decreased ability of chondrocytes to restore or maintain the articular cartilage, and 3) decreasing articular surface contact stress will decrease the risk of post-traumatic OA and provide effective treatment for ankle OA. The specific projects will include: 1) a prospective clinical study to define the relationships between acute energy absorption and chronic articular surface contact stress and the risk of post-traumatic ankle OA, 2) a prospective clinical study of the effects of decreasing articular surface contact stress in osteoarthritic ankles, 3) basic scientific and experimental investigations of the pathogenesis of post-traumatic CIA, and 4) basic in vitro investigations of the effects of age and mechanically induced oxidative stress on chondrocyte senescence and the effects of anti-oxidant defenses on chondrocyte senescence. These projects will contribute significantly to the understanding of the pathogenesis of post-traumatic CIA and will lay the foundation for new methods of preventing and treating this disease, as well as other forms of CIA. As a result of the integrated multi-disciplinary scientific approach focused on a well-defined research theme, this SCOR will create a national resource for rapid advancements in the understanding of the pathogenesis, prevention, and treatment of post-traumatic OA.